CN108864174B - Tris (o-chlorobenzyl) tin salicylate, preparation method and application thereof - Google Patents
Tris (o-chlorobenzyl) tin salicylate, preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses tri (o-chlorobenzyl) tin salicylate, which is a compound with the following structural formula. The invention selects tri (o-chlorobenzyl) stannic chloride and ligand salicyloyl to react under certain conditions, and compounds tri (o-chlorobenzyl) stannic salicylate with stronger inhibitory activity to human breast cancer cell (MCF7) cell strain, human lung cancer cell (A549) and human lung cancer cell (H460) are synthesized, thus providing a new approach for developing anticancer drugs. The tri (o-chlorobenzyl) tin salicylate complex has a certain thermal stability range, and can stably exist at the temperature of below 205 ℃.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to tri (o-chlorobenzyl) tin salicylate and a preparation method and application thereof.
Background
The organic tin is a metal organic compound containing Sn-C bonds, has higher bioactivity, and has wide application prospects in the fields of sterilization, disinsection, preparation of anticancer drugs and the like. The existing research shows that the alkyl R in the organic tin is the main factor for determining the anticancer activity of the compound, for example, the cyclohexyl, n-butyl and phenyl tin compounds have stronger anticancer activity, and the methyl has almost no anticancer activity. The structure of the ligand plays an important role in the anticancer activity of the complex and the broad spectrum of killing cancer cells, and experiments prove that the biological activity of the organotin carboxylate complex is often higher than that of a corresponding organotin compound.
Chinese patent CN 103483374B discloses the application of tributyltin organic acid ester coordination polymer in preparing drugs for treating cervical cancer, breast cancer, liver cancer, colon cancer and lung cancer.
Chinese patent CN 103087115B discloses the application of ferrocenyl tributyltin benzoate coordination polymer in preparing medicines for treating nasopharyngeal carcinoma, breast cancer, liver cancer, colon cancer and lung cancer.
Chinese patent CN 103467512B discloses the application of large-ring two-dimensional net structure tributyltin pyromellitic acid ester in preparing medicine for treating cervical cancer, breast cancer, liver cancer, colon cancer and lung cancer.
Chinese patent CN 103087115B discloses the application of ferrocenyl tributyltin benzoate coordination polymer in preparing medicines for treating nasopharyngeal carcinoma, breast cancer, liver cancer, colon cancer and lung cancer.
Disclosure of Invention
One of the technical problems to be solved by the present invention is to provide tris (o-chlorobenzyl) stannic salicylate.
The second technical problem to be solved by the present invention is to provide a method for preparing tris (o-chlorobenzyl) stannic salicylate.
The invention also provides an application of the tri (o-chlorobenzyl) tin salicylate.
The tri (o-chlorobenzyl) tin salicylate as the first aspect of the present invention is a compound of the following structural formula:
in a preferred embodiment of the invention, the tris (o-chlorobenzyl) stannyl salicylate has a crystal structure, the crystal of which belongs to the triclinic system, space group
The crystallographic parameters are as follows: a is 1.11015(12) nm, b is 1.11561(12) nm, c is 1.13231(12) nm, α is 90.9560(10) °, β is 103.3300(10) °, γ is 100.2140(10) °, Z is 2, V is 1.3405(2) nm3，Dc＝1.567Mg·m-3(ii) a The central tin atom coordinates with three carbon atoms and one oxygen atom, forming a distorted tetrahedral configuration.
In a preferred embodiment of the present invention, the infrared spectrum data of the tris (o-chlorobenzyl) tin salicylate is as follows: IR (KBr, cm)-1)：3055.25，2978.09，2943.38，2902.87，2877.80(νC-H)，1633.71[νas(COO)]，1390.68[νs(COO)]，673.16(νSn-O)，430.13(νSn-C)。
The preparation method of tris (o-chlorobenzyl) tin salicylate as the second aspect of the invention is that tris (o-chlorobenzyl) tin chloride, salicylic acid, triethylamine and a proper amount of methanol with equal molar ratio are added into a container and reacted for 10 hours under stirring and refluxing; cooling and filtering; controlling the solvent to volatilize and crystallize at the temperature of 25-35 ℃ to obtain a colorless transparent crystal, namely the tri (o-chlorobenzyl) tin salicylate.
The application of the tri (o-chlorobenzyl) stannum salicylate as the third aspect of the invention is the application in preparing the medicine for treating cancer.
In a preferred embodiment of the invention, the cancer is breast cancer or lung cancer.
The invention selects tri (o-chlorobenzyl) stannic chloride and ligand salicyloyl to react under certain conditions, and compounds tri (o-chlorobenzyl) stannic salicylate with stronger inhibitory activity to human breast cancer cell (MCF7) cell strain, human lung cancer cell (A549) and human lung cancer cell (H460) are synthesized, thus providing a new approach for developing anticancer drugs. The tri (o-chlorobenzyl) tin salicylate complex has a certain thermal stability range, and can stably exist at the temperature of below 205 ℃.
Drawings
FIG. 1 is a schematic diagram of the crystal molecular structure of tris (o-chlorobenzyl) tin salicylate of the present invention.
FIG. 2 is a TG-DTG graph of tris (o-chlorobenzyl) tin salicylate of the present invention.
Detailed Description
The tri (o-chlorobenzyl) tin salicylate of the invention is a compound with the following structural formula:
the preparation method of the tri (o-chlorobenzyl) tin salicylate comprises the following steps: in a 100mL round bottom flask, 1.062g (2mmol) of tri-o-chlorobenzyl tin chloride, 0.277g (2mmol) of salicylic acid, 0.203g (2mmol) of triethylamine and 50mL of methanol are added, and the mixture is reacted for 10 hours under stirring and refluxing; cooling and filtering; controlling the solvent to volatilize and crystallize at the temperature of 25-35 ℃ to obtain 1.03g of colorless transparent crystals with the yield of 81%.
Melting point of the above tris (o-chlorobenzyl) tin salicylate: 93-95 ℃.
IR (KBr, cm) of the above tris (o-chlorobenzyl) tin salicylate-1)：3055.25，2978.09，2943.38，2902.87，2877.80(νC-H)，1633.71[νas(COO)]，1390.68[νs(COO)]，673.16(νSn-O)，430.13(νSn-C)。
Elemental analysis (C) of tris (o-chlorobenzyl) tin salicylate28H23Cl3O3Sn), calculated (%): c, 53.17; h, 3.67. Found (%): c, 53.23; h, 3.61.
The crystal molecular structure of the tris (o-chlorobenzyl) tin salicylate is shown in figure 1, and the crystallographic data thereof are as follows: the crystal belongs to the triclinic system, space group
The crystallographic parameters are as follows: a is 1.11015(12) nm, b is 1.11561(12) nm, c is 1.13231(12) nm, α is 90.9560(10) °, β is 103.3300(10) °, γ is 100.2140(10) °, Z is 2, V is 1.3405(2) nm3，Dc＝1.567Mg·m-3(ii) a The central tin atom coordinates with three carbon atoms and one oxygen atom, forming a distorted tetrahedral configuration.
The tri (o-chlorobenzyl) tin salicylate complex has a certain thermal stability range, and can exist stably at the temperature of below 205 ℃ (see figure 2).
Antitumor activity test of the tris (o-chlorobenzyl) tin salicylate
Test solutions (0.1nM-10uM) were added to each well according to concentration gradients, with 6 parallel wells per concentration. The experiment was divided into drug test group (with different concentrations of test drug added), control group (with culture medium and cells only, without test drug added) and blank group (with culture medium only, without cells and test drug added). Placing the medicated hole plate at 37 deg.C and 5% CO2Culturing for 72h in an incubator. The activity of the control drug was determined as per the method of the test sample. MTT40uL (4 mg/mL using D-Hanks buffer) was added to each well after 72h incubation.After standing at 37 ℃ for 4h, the supernatant was removed. 150uLDMSO is added into each hole, and oscillation is carried out for 5min, so that the Formazan crystal is dissolved. Finally, the optical density of each well was measured at a wavelength of 570nm using an automatic microplate reader.
Data processing: data processing Using the Graph Pad Prism version5.0 program, Compound IC50Fitting was done by a non-linear regression model with sigmoidal dose response in the program.
The human breast cancer cell (MCF7) cell line, human lung cancer cell (A549) and human lung cancer cell (H460) cell line were analyzed by MTT assay, and IC was determined50The results are shown in table 1, with the conclusion that: as can be seen from the data in the table, the anticancer drug of the invention has higher anticancer activity to human breast cancer and human lung cancer, and can be used as a candidate compound of the anticancer drug.
TABLE 1 Tri (o-chlorobenzyl) stannate salicylate complex anticancer drug in vitro activity test data
| Human breast cancer cell | Human lung cancer cell | Human lung cancer cell | |
| Cell line | MCF-7 | A549 | H460 |
| IC50μM | 0.22 | 0.20 | 0.43 |
Claims (3)
1. A tris (o-chlorobenzyl) tin salicylate, characterized by being a compound of the following structural formula:
the tris (o-chlorobenzyl) stannyl salicylate has a crystal structure, and the crystal belongs to a triclinic system and a space group
The crystallographic parameters are as follows: a is 1.11015(12) nm, b is 1.11561(12) nm, c is 1.13231(12) nm, α is 90.9560(10) °, β is 103.3300(10) °, γ is 100.2140(10) °, Z is 2, V is 1.3405(2) nm3，Dc＝1.567Mg·m-3(ii) a The central tin atom is coordinated with three carbon atoms and one oxygen atom to form a distorted tetrahedral configuration; the infrared spectrum data of the tri (o-chlorobenzyl) tin salicylate are as follows: IR (KBr, cm)-1)：3055.25，2978.09，2943.38，2902.87，2877.80(νC-H)，1633.71[νas(COO)]，1390.68[νs(COO)]，673.16(νSn-O)，430.13(νSn-C)。
2. The method for preparing tris (o-chlorobenzyl) tin salicylate of claim 1, wherein the tris (o-chlorobenzyl) tin salicylate is prepared by adding tris (o-chlorobenzyl) tin chloride, salicylic acid, triethylamine and a proper amount of methanol in an equal molar ratio into a container, and reacting for 10h under stirring and refluxing; cooling and filtering; controlling the solvent to volatilize and crystallize at the temperature of 25-35 ℃ to obtain a colorless transparent crystal, namely the tri (o-chlorobenzyl) tin salicylate.
3. The use of tris (ortho-chlorobenzyl) stannyl salicylate of claim 1 for the manufacture of a medicament for the treatment of cancer, wherein the cancer is breast cancer or lung cancer.
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Citations (4)
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| CN104177402A (en) * | 2014-07-23 | 2014-12-03 | 衡阳师范学院 | Polysubstituted benzoic acid organotin complex, and preparation method and application thereof |
| CN106967109A (en) * | 2017-03-29 | 2017-07-21 | 衡阳师范学院 | One-dimensional picolinic acid ester complex of two (o-chlorobenzyl) stannic chloride 2 and preparation method and application |
| CN107011375A (en) * | 2017-03-29 | 2017-08-04 | 衡阳师范学院 | A kind of double [chlorination two (o-chlorobenzyl) tin thiosalicylic acid butyl ester complexs] and preparation method and application |
| CN107602606A (en) * | 2017-09-18 | 2018-01-19 | 衡阳师范学院 | A kind of three (adjacent bromobenzyl) tin salicylate complexs and preparation method and application |
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|---|---|---|---|---|
| CN104177402A (en) * | 2014-07-23 | 2014-12-03 | 衡阳师范学院 | Polysubstituted benzoic acid organotin complex, and preparation method and application thereof |
| CN106967109A (en) * | 2017-03-29 | 2017-07-21 | 衡阳师范学院 | One-dimensional picolinic acid ester complex of two (o-chlorobenzyl) stannic chloride 2 and preparation method and application |
| CN107011375A (en) * | 2017-03-29 | 2017-08-04 | 衡阳师范学院 | A kind of double [chlorination two (o-chlorobenzyl) tin thiosalicylic acid butyl ester complexs] and preparation method and application |
| CN107602606A (en) * | 2017-09-18 | 2018-01-19 | 衡阳师范学院 | A kind of three (adjacent bromobenzyl) tin salicylate complexs and preparation method and application |
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